Effects of transforming growth factor-β3 and matrix metalloproteinase-3 on the pathogenesis of chronic mitral valvular disease in dogs

• DOI: 10.2460/ajvr.72.2.194
• Publication Date: 2011-02-01T08:03:28Z
• Authors: Koji Obayashi; Sachiko Miyagawa-...; Hirotaka Matsumoto; Hidekazu Koyama; Toshio Nakanishi; Hisashi Hirose
• Keywords: Pathogenesis; Mitral valve prolapse; valvular heart disease

Abstract Objective —To investigate the roles of transforming growth factor-β (TGF-β) isoforms and matrix metalloproteinases (MMPs) in development chronic mitral valvular disease (CMVD) dogs. Sample Population —12 valve leaflets collected from cadavers 5 clinically normal dogs 7 with CMVD. Procedures —Expression TGF-β 1, 2, 3; MMPs 3, 9; receptor II (TβR-II); α smooth muscle actin (αSMA) valves CMVD was compared that Additionally, responses interstitial cells (VICs) to TGF-β3, MMP-3, angiotensin-converting enzyme inhibitor (ACEI) as a suppressor TGF-β3 were examined vitro. Results TβR-II, αSMA, MMP-3 only detected Concentrations αSMA proteoglycans cultured VICs significantly increased following incubation TGF-β3; treatment resulted amounts active total decreased by ACEI. Conclusions Clinical Relevance —Findings suggested contribute pathogenesis degeneration associated In addition, it is possible use ACEI could effectively block pathological alterations Impact on Human Medicine —CMVD primary prolapse Marfan syndrome humans. study reported here will help elucidate molecular mechanisms